Retroviruses integrate a DNA copy of their genome into host DNA as an obligatory step in their replication cycle. Recent work focusses on the structure and function of HIV integrase, the viral enzyme that catalyzes insertion of the viral DNA into the host chromosome. The N- terminal domain of this enzyme binds zinc with a stoichiometry of one zinc per monomer. In the absence of zinc, the isolated N-terminal is disordered, but in the presence of zinc it adopts a structure with a high alpha helical content as judged by circular dichroism. The solution structure of this domain is currently being studied in collaboration with the Gronenborn and Clore laboratories in LCP/NIDDK. The structure of the catalytic core domain and the C-terminal DNA binding domain of HIV integrase have previously been determined by X- ray crystallography and NMR; efforts to obtain diffracting crystals of the intact protein are in progress. Other aspects of retroviral DNA integration are studied with Moloney murine leukemia virus as a model system. The viral DNA made by reverse transcription exists as part of a high molecular weight nucleoprotein complex derived from the core of the infecting virion. The viral DNA within this complex is protected from self-destructive integration into itself (autointegration). A cellular protein is responsible for conferring the protection. This protein has been purified from NIH3T3 cells using in vitro reconstitution of the autointegration barrier as an assay.